In many vertebrates, intraspecies signals have been shown to alter social and/or endocrine-related behaviors. These chemosensory signals are thought to be detected and processed by specialized receptor cells (bipolar neurons) of the vomeronasal (VN) organ. The function of the VN organ has been thought to be exclusively linked to pheromone stimulation, however, a variety of data has accumulated to suggest that the VN organ also detects general odors. To date, definitive experiments elucidating such actions on individual VN bipolar neurons have not been performed. The overall objective of this grant proposal is to determine the precise mechanism(s) involved in the detection and transduction of pheromone and/or general odor signals in isolated mouse VN bipolar neurons. Four specific aims are proposed. First is to characterize the electrophysiological, biophysical and pharmacological properties of VN bipolar neurons in the absence of pheromones and general odorants. Whole-cell voltage- and current-clamp recordings will be made at the soma to study the generic membrane properties of VN bipolar receptor neurons. Second is to determine the kinetic properties of pheromone and general odor-induced currents. Here species specific pheromones and general odorants will be applied via a puffer pipette to the dendrite, while recordings from the soma of the same bipolar neuron will be made under whole-cell voltage- and current-clamp mode. Third is to determine the effects of non-genomic and genomic actions of steroids on the kinetics of pheromone- and general odor-induced currents recorded under whole-cell voltage- and current-clamp configuration. Fourth is to determine the role of the cyclic nucleotides in the pheromone- and odor-induced currents in VN bipolar neurons. Pheromones and odors will be applied via puffer pipette while recordings will be made under whole-cell, cell- attached and inside-out patch configuration to dendrites of VN bipolar neurons. The completion of these studies will provide a basic foundation for understanding how pheromone signals are detected and how this information is transduced into electrical events for subsequent transmission to the central nervous system. The results could also provide information relevant to our basic understanding of the cellular events underlying intraspecies communication, emotions and feelings as well as psychiatric/endocrine abnormalities such as bipolar disorder (mood swings) and Kallmann's syndrome.